Transitions of blood immune endotypes and improved outcome by anakinra in COVID-19 pneumonia: an analysis of the SAVE-MORE randomized controlled trial.

BACKGROUND: Endotype classification may guide immunomodulatory management of patients with bacterial and viral sepsis. We aimed to identify immune endotypes and transitions associated with response to anakinra (human interleukin 1 receptor antagonist) in participants in the SAVE-MORE trial. METHODS: Adult patients hospitalized with radiological findings of PCR-confirmed severe pneumonia caused by SARS-CoV-2 and plasma-soluble urokinase plasminogen activator receptor levels of ≥ 6 ng/ml in the SAVE-MORE trial (NCT04680949) were characterized at baseline and days 4 and 7 of treatment using a previously defined 33-messenger RNA classifier to assign an immunological endotype in blood. Endpoints were changes in endotypes and progression to severe respiratory failure (SRF) associated with anakinra treatment. RESULTS: At baseline, 23.2% of 393 patients were designated as inflammopathic, 41.1% as adaptive, and 35.7% as coagulopathic. Only 23.9% were designated as the same endotype at days 4 and 7 compared to baseline, while all other patients transitioned between endotypes. Anakinra-treated patients were more likely to remain in the adaptive endotype during 7-day treatment (24.4% vs. 9.9%; p < 0.001). Anakinra also protected patients with coagulopathic endotype at day 7 against SRF compared to placebo (27.8% vs. 55.9%; p = 0.013). CONCLUSION: We identify an association between endotypes defined using blood transcriptome and anakinra therapy for COVID-19 pneumonia, with anakinra-treated patients shifting toward endotypes associated with a better outcome, mainly the adaptive endotype. Trial registration ClinicalTrials.gov, NCT04680949, December 23, 2020.

Antibiotic Stewardship in Surgical Departments.

Antimicrobial resistance (AMR) has emerged as one of the leading public health threats of the 21st century. New evidence underscores its significance in patients' morbidity and mortality, length of stay, as well as healthcare costs. Globally, the factors that contribute to antimicrobial resistance include social and economic determinants, healthcare governance, and environmental interactions with impact on humans, plants, and animals. Antimicrobial stewardship (AS) programs have historically overlooked surgical teams as they considered them more difficult to engage. This review aims to summarize the evolution and significance of AS in surgical wards, including the surgical intensive care unit (SICU) and the role of diagnostic stewardship (DS). The contribution of AS team members is presented. The new diagnostic modalities and the new technologies including artificial intelligence (AI) are also reviewed.

HEPARIN-BINDING PROTEIN LEVELS PREDICT UNFAVORABLE OUTCOME IN COVID-19 PNEUMONIA: A POST HOC ANALYSIS OF THE SAVE TRIAL.

ABSTRACT: We aimed to evaluate heparin-binding protein (HBP) as a marker of prognosis of unfavorable outcome in COVID-19 pneumonia. This was a post hoc analysis of the SAVE clinical trial investigating anakinra treatment, guided by suPAR (soluble urokinase plasminogen activator receptor) levels ≥6 ng/mL, for the prevention of severe respiratory failure in hospitalized patients with COVID-19 pneumonia. Baseline HBP plasma levels were measured in 534 patients by fluorescence dry quantitative immunoassay using the Jet-iStar 800 analyzer. Concentrations higher than 35 ng/mL predicted 30-day mortality with a moderate specificity of 53.3% and negative predictive value 78.1%; sensitivity was low (29.0%). After multivariate Cox analysis, HBP higher than 35 ng/mL was an independent predictor of 30-day unfavorable outcome (adjusted hazard ratio, 1.77; 95% CI, 1.06-2.94; P = 0.028) and these patients were also at greater risk of death after 90 days (hazard ratio, 1.85; 95% CI, 1.25-2.74; P = 0.002). The cutoff was not predictive of development of severe respiratory failure, septic shock or acute kidney injury. Among patients with baseline HBP levels higher than 35 ng/mL, anakinra treatment was associated with decreased mortality (7.2%) versus comparators (18.1%; P < 0.001). Results confirm that HBP may be an early biomarker of poor outcome among preselected patients at risk from COVID-19 pneumonia.ClinicalTrials.gov registration NCT04357366.

COVID-19 in Patients with Melanoma: A Single-Institution Study.

We conducted a single-center, non-interventional retrospective study of melanoma patients with COVID-19 (1 March 2020 until 17 March 2023). The cohort was further divided into three groups according to the periods of SARS-CoV-2 variant dominance in Greece. We recorded demographics, comorbidities, vaccination data, cancer diagnosis/stage, types of systemic melanoma treatments, date of COVID-19 diagnosis and survival. We identified 121 patients. The vast majority (87.6%) had advanced disease (stages III or IV). A total of 80.1% of the patients were receiving immune checkpoint inhibitor-based therapies, 92.5% had asymptomatic/mild COVID-19 and 7.4% had moderate/severe/critical disease, while 83.5% contracted COVID-19 during the third period of the pandemic. Sixteen patients (13.2%) were hospitalized for COVID-19 with a median length of stay of 12 days (range: 1-55 days). Advanced age, heart failure, number of comorbidities (≤1 vs. >1), vaccination status and the time period of the infection correlated with more severe COVID-19, whereas only heart failure and time period were independently correlated with severity. The 30-day mortality rate after COVID-19 was 4.2%. With a median follow-up of 340 days post-COVID-19, 17.4% of patients were deceased. In this cohort of melanoma patients with COVID-19, the 30-day mortality rate was low. There was no association between melanoma stage, treatment receipt and type of treatment with COVID-19 severity.